Synthesis, Acute Toxicity, and Analgesic Activity of New Derivatives of Pyrrole

Abstract

Ten pyrrole derivatives (including six new compounds) were synthesized and evaluated as potential platform for analgesic agents' development. Acute intraperitoneal toxicity and analgesic activity studies (acetic acid writhing test) were performed on mice with acetylsalicylic acid used as a reference substance. Products 3c, 3d, 3e, and 3h exhibited a dose-dependent activity demonstrating 1.5 to 2.5-fold better protections than the reference. The most prospective compounds comprised salicylic acid moieties, whose 4-substituted derivatives were related to lower acute toxicity and considerable activity. 4-[3-(Ethoxycarbonyl)-2-methyl-5-(3,4-dimethoxy-phenyl)-1H-pyrrol-1-yl]-2-hydroxy-benzoic acid 3c was pointed out as the most prospective substance due to its lower acute toxicity (378 mg/kg body weight, intraperitoneally) and highest analgesic activity (up to 89.3% protection) in a dose range of 1/10 to 1/40 parts of LD(50).

Synthesis Strategies and Biological Value of Pyrrole and Pyrrolopyrimidine

“…In 2006, Danchev et al 8 applied Paal-Knorr cyclization between intermediately prepared 1,4dicarbonyl compounds and different aryl amines to afford pyrrole 8.…”

In Vivo Evaluation of Anti-inflammatory Activity of 2-[3-Acetyl- 5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-4-methylsulfanylbutyric Acid

“…The chemistry, design, synthesis and characterization by spectroscopy and TLC (thin line chromatography) were described by Vladimirova et al 7 The pyrrolic ring is chosen as a central core due to the involvement of this heterocycle in the pharmacophore system of a large number of classic and contemporary NSAIDs. [8][9][10] The structure of the target molecule is oriented to the architecture of the selected prototype for a contemporary antiinfl ammatory agent celecoxib (a selective COX-2 inhibitor), thus expecting manifestation of its characteristic pharmacological activity. Th e carrageenan model chosen in this study is generally used to assess potential anti-infl ammatory activity of novel substances.…”

Synthesis and Structure Activity Relationship of Some Indole Derivatives as Potential Anti-inflammatory Agents

“…[11][12][13] Structural variation of the heterocyclic rings through the manipulation of the heterocyclic core influences the activity of the resulting fused systemes, among these of pyrroles and their fused deivatives. [14][15][16] Due to their pharmaceutical importance, [17][18][19][20][21][22] attention was paid to develop a new synthetic route for pyrroles and their fused forms. [23][24][25][26][27][28] Pyrrolylacetic acid derivatives such as tolmetin (Rumatol ® ) and zomepirac (Zomax ® ) were proved to be NSAIDs 6 with strong anti-inflammatory activity.…”